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Friday, April 27, 2012

If you're into this sort of thing, as I am, an entertaining review just came out in the journal Sports Medicine [media summary], detailing all the skin disorders that Olympic athletes must contend with in addition to trying to beat Michael Phelps or Usain Bolt or any Kenyan marathoner or Cuban boxer. Boy, are there a lot of weird dermatoses out there. Jogger's nipples, rower's rump, cauliflower ear, green hair, swimmer's itch, seabather's eruption, talon noir, jellyfish stings.

Contact dermatitis is a popular one. You run the risk of getting it in all the fighting sports--judo, wrestling, boxing--as well as many of the team sports.

Eczema gets hardly a mention--save for one interesting fact the authors, Jacqueline De Luca of the University of Hawaii and colleagues, mention. "Pre-existing dermatoses can also be aggravated with practice and competition," they say. "This is especially problematic given the fact that prevalence of eczema and atopy are higher in the elite athlete population."

Cool, so eczema makes me more athletic then!

Well, not really. The authors' reference is this article, which was written in advance of the 2008 Beijing Games and mostly considers asthma with only a brief nod to eczema. There was a lot of worry about air pollution at those Games, I remember. The older article points out a higher incidence of asthma in elite athletes, and attempts to explain why--perhaps extreme exercise, with its high air intake, increases allergic sensitization.

So being athletic puts you at higher risk of getting asthma. I'm not very athletic...maybe that's what saved me from becoming asthmatic. Looking on the bright side!

Wednesday, April 25, 2012

Of course I know this, but last week I got a vivid reminder when both my kids came down with different rashes at the same time.

Shmoop had had a fever that peaked at 104F a few days before. Then, on the day before our planned trip to Lake Tahoe (naturally), he suddenly became itchy all over. Wherever he scratched, a red wheal appeared, with raised white welts. Soon he was covered head to toe in something that a cartoonist might have drawn to caricature a sick kid.

Voov, the one who has eczema, developed pinpoint dark red speckles on her arms and cheeks.

I made same-day appointments, took time off work, and drove the kids to the doctor. In the waiting room, as the kids played with toys they found there, I became aware once again that there is probably no better place than a pediatric waiting room to expose yourself to virulent pathogens.

Shmoop had the first appointment. The doctor looked him over and said that the rash was probably the result of his having a fever beforehand. Kids apparently are prone to getting rashes after fevers. Shmoop probably wasn't contagious...anymore. She prescribed Atarax (hydroxyzine HCl) as an anti-itch, and prednisolone if that didn't work. (We'd tried children's Benadryl without success.)

As I type this, I realize that I didn't check out all the side effects of Atarax. It's also used "for the short-term treatment of nervousness and tension that may occur with certain mental/mood disorders (e.g., anxiety, dementia)." It worked immediately to bring the rash down, which was great. It's also great that we got him off it asap. The idea of your kid being on a mood medication is disturbing.

Voov had the second appointment, with a different doctor. "That's hand, foot, and mouth," she announced confidently without even looking closely at the rash. As it turns out, it wasn't. Upon examining it, she said she didn't know what it was, but that Benadryl would probably work. And that kids get all kinds of rashes and this one didn't look like anything serious.

This sounded fine to me. I worry less than I should about things, to make up for my wife, Hidden B, worrying more than she should. Voov's rash did clear up, after briefly spreading to her face.

Through this experience I realized why people who see your eczema often react the way they do: avoid contact, pull their kids away from yours. They don't know what's causing the rash, or if it's contagious.

And neither do doctors. Pediatricians, especially, often have no idea why your kid is sick. And doctors in general often have no idea what is causing a skin problem for anyone, adult or child. The combination of kid & rash makes for maximum uncertainty. Eczema is not the only rash, nor the only rash of which doctors don't know the cause or cure. This is something we have to accept, difficult as it is, as the current state of medicine.

There’s about a 30% chance the cream inside an open jar or tube is contaminated with some microbes, although the actual number of organisms is likely relatively small. The chance is twice as high that microbes are teeming on the rim of the container, say Michael Lundov and colleagues at the University of Copenhagen, who conducted the study.

I probably don't need to point out that if your cream or ointment is in a tube, the only way it comes out is past the rim.

The authors used industry standard techniques to culture bacteria, fungi, and yeast from 32 different hand cream products collected from 20 patients. They transferred small samples of the creams to agar plates and counted the number of microbial colonies that grew.

"It is important that the patients exercise care in using creams and limit contact between the opening/edge of the container and their skin," the authors say.

They did not include a control from an unopened jar or tube, which would be interesting because it would indicate how sterile their method was. In the paper they report only that colonies grew in 20 of the 32 tests, but they count the presence of very small numbers of colonies as an indication the hand cream was contaminated. So things may not be as bad as they appear.

What can you do to prevent contamination? In biology, it’s common to take a large quantity of a reagent and parcel it out into small “aliquots.” Then you use one aliquot at a time so you don’t run the risk of contaminating the whole batch. Now, I don’t want to do that with my jumbo jar of Eucerin, but the authors suggest that I might want to use a sterile-ish spoon to take cream out each time I use it—presumably without then putting the spoon back in. I know this method is practical because Nikki, a Twitter user, told me she does this at home.

Saturday, April 14, 2012

Anacor Pharmaceuticals, a company located near me in the Bay Area, has two interesting drug candidates in the pipeline to treat eczema. I've been meaning to review them for a while--at first I thought I needed to speak to someone at Anacor, but then I realized that a lot of the information is online and if I did manage to hear from an Anacor rep I'd probably only get a bland corporate response. (Ideally you want to hear criticism from a competitor to get the real dirt!)

The two compounds, AN2728 and AN2898, are also in clinical trials for treatment of psoriasis--the trials for psoriasis are a couple substages ahead of those for eczema. Look at the structures--you can see they are closely related compounds. They both inhibit the enzyme phosphodiesterase IV (PDE4). PDE4's job (it's primarily found in white blood cells) is to break a bond in a signaling molecule called cyclic AMP (cAMP). Although cAMP participates in all kinds of processes in the body, in white blood cells it turns off inflammation. So if you inhibit the enzyme that breaks down cAMP, you inhibit inflammation.

So Anacor's compounds, which I believe are in trials as topical creams, could be an alternative to corticosteroids. Clinical trials in humans will show whether AN2728 and AN2898 have more or fewer side effects than steroids.

I find Anacor interesting because it's local, for me, and because boron compounds are chemically unusual in biology. Boron can form either three or four bonds with neighboring atoms, and while carbon can also do this (two single bonds and one double bond), Anacor says that using boron in their compounds lets them make molecules that can interact with enzymes in unusual ways that carbon compounds cannot.

A small contingent of medical chemists seems to be cheering Anacor on just because boron compounds are cool. It's like mechanics who love the Wankel rotary engine in the Mazda RX-7 because it works differently from engines in most other cars. But the ultimate test is whether these compounds work. It would be nice to have another topical option to reduce inflammation and itch.

Even if they do work, they'll only be treating the local symptom of the disease and not its cause or systemic origin. But, in their favor, that is how Protopic and Elidel work--when they DO work.

It's been known for a while that exposure to certain microbes, particularly on farms, seems to protect children against eczema to some degree. The microbes must contain, or be coated in, some active compounds that cause the immune system to develop tolerance; researchers have identified a number of classes of compounds, including those called lipopolysaccharides and peptidoglycans. In this recent trial, involving over 600 subjects, the scientists used whole-cell extracts from heat-inactivated Escherichia coli and Enterococcus faecalis. They asked parents to dose their kids three times daily from the age of 5 weeks to 7 months.

Parents were selected for the trial if one or both had a history of eczema, asthma, or allergic rhinitis. Overall, the treatment had no effect on whether or not the children developed eczema. However, when the scientists considered children who only had one parent with atopy, the treatment reduced the kids' chances of developing eczema from 19% to 10% (measured right at the end of the trial; the improvement was lasting, up to three years out). The effect was even more pronounced if it was the dad, rather than the mom, who was atopic; the risk dropped from 32% to 11%.

Now I'd like to know why the children of atopic dads had a 32% chance of getting eczema, versus 19% for children who had either an atopic mom or dad. I can't find an explanation in the paper.

Instead, the authors focus on why the improvement was weaker in the atopic either-mom-or-dad group. They suggest that this is because a fetus's immune system depends not just on its genetics but also a heavy imprint that the fetus receives from the mother during pregnancy. If the mom is atopic, dosing the infant with bacteria after birth has less influence on whether he or she develops eczema. If the dad is atopic, the medicine has a stronger effect.

This seems contradictory to me; if the maternal imprint has a major effect, the children of parents of whom only the mom is atopic should be more likely to develop eczema than the children of parents of whom only the dad is atopic. The authors say that this is indeed the fact, but their own paper has it the other way around.

The inactivated-bacteria therapy is well-documented as safe, the authors say; it has been used to treat irritable bowel syndrome. In this trial they saw very few adverse reactions.

Do you think that parents of newborns would be likely to use this treatment on their kids? I wonder. Only if you've lived with severe eczema, or already had a child with it, or seen it close up, would you be motivated at the very difficult early months to try to give your kid medicine. And you could say it roughly halves the chances of developing eczema, but in truth, it reduces it from 20% to 10%. If this study is true, that's what you get for six months of giving your kid medicine three times a day. Would you do that if only one parent had hayfever?

Friday, April 6, 2012

Look for my blog posts to appear regularly, if sparsely, on the website of the US's National Eczema Association starting soon. That was the upshot of a trip I took today with my 3-year-old daughter Voov to meet the NEA's CEO Julie Block at the organization's headquarters in San Rafael, California--which is only a 20-minute drive from where I live. Isn't it convenient!

Voov, Spanish Key (in disguise w/ late-phase Miles Davis wig), and a concerned-looking Julie Block, CEO of the National Eczema Association, at the nonprofit's HQ in San Rafael. Like the logo on the door? It's part of the NEA's recent rebranding effort.

About two years ago, when I was starting this blog, I talked to Julie and NEA communications director Diane Dunn about how we might be able to partner. I work at a dynamic bioscience campus in San Francisco, and I was hoping Julie and Diane might come down for a tour, to see how eczema therapies might be commercialized; but it wasn't happening. And if the mountain won't come to Mohammed, Mohammed must go to the mountain. Opportunity arose this week when I had to stay home on Friday to look after Voov.

Voov inherited my genes for eczema. She gets it on her hands--red, crusty inflammation and cracks that won't heal. But she's good-spirited. During today's summit she entertained herself with Julie's collection of binder clips and colored markers, and afterward sang "Jingle Bells" most of the way home.

Julie and I had a great two-hour conversation about eczema science writing, blogging, social media, and nonprofit fundraising. We agreed that eczema is covered only very shallowly in the mass media, despite 20% of children being affected and 2-3% of adults. There's a need for information about causes and treatment. Likewise, the blogosphere has very few voices covering eczema. On the web in general, overly commercial sites touting treatments of dubious worth tend to dominate. By contrast, the NEA provides a credible forum on its website where patients and parents can go to get scientifically valid information about eczema. Julie is particularly proud of the NEA's Facebook page, which enables them to engage almost in real-time with the community; she's happy, though, that a number of more conservative (not in the political sense) users tamp down the emotion and opinions that eczema can churn up.

Supporting basic and applied eczema research is a priority for the NEA, which offers a limited number of grants at the smaller end of the spectrum (around $100k). Julie points out that winning such grants, from a patient advocacy organization, can make a scientist's application for larger grants much more attractive to the NIH. In my day job, I also see the effect that "smaller" grants can have if given at the crucial precommercial stage where a scientist is doing experiments to validate research before spinning off a company. It's with the broad goal of raising donations for the NEA to fund research that I'm going to be writing blog posts for the NEA website (probably every month or two). As I do on this blog, I'll be covering recent advances in the field, showing that the field is active: steroids, Protopic, and Elidel are not the best that science can do for eczema patients. Things will get better in the future, and it's up to people like us to make it happen sooner rather than later.

(What's up with that wig in the photo? The NEA shares office space with the National Alopecia Areata Foundation, which has a surplus of wigs generously donated by Revlon. I'm balding and wanted to feel, just for a moment, what it was like to have a glorious head of hair.)

Wednesday, April 4, 2012

This past week researchers published a paper [media summary] that helps clarify the connection between gut bacteria and the type of system-wide allergic inflammation responsible for asthma and, often, eczema.

David Artis and colleagues at the University of Pennsylvania (the team includes members from Japan and Germany) find that killing off gut bacteria in mice, using antibiotics, results in much higher levels of IgE antibodies and increased populations of basophils, a type of white blood cell involved in allergic inflammation.

Trillions of commensal bacteria live in our intestines, along with other types of less-numerous microbes. Decreases in numbers or diversity of these bacteria are associated, in children, with increased risk of developing allergic disease. Commensal microbes help us digest our food. They are integrated into other processes as well, including the immune system. They have to be. They need to suppress immune reactions that would otherwise destroy them.

Artis and colleagues pointed out that high IgE levels are associated with increased basophil populations in human patients with "hyperimmunoglobulinemia E syndrome," who are at high risk of developing eczema.

The researchers weren't able to specify which species of bacteria are most important in regulating IgE and basophils, but they did show that chemical signals from commensal bacteria normally limit the number of basophils that develop from the bone marrow.

This research supports the idea that overuse of antibiotics in children makes them more likely to develop atopic disease. Far in the future, this work could result in anti-inflammatory therapies based on the chemical signals that gut bacteria use to suppress basophils.